Beta-Thalassemia major (thalassemia) is a common genetic condition causing profound anemia which is very widespread in the world, particularly in countries where malaria has been prevalent, because single copies of the gene, which are insufficient to cause the major disease, offer protection against malaria. Some 93 million worldwide carry one copy of this gene, and one-quarter of children will inherit the major condition if 2 carriers reproduce. About 60,000 children are born annually with thalassemia and treatment is invasive and expensive. Regular blood transfusions are required to keep the children alive, but this leads to iron overload in the tissues which causes death at a young age in many sufferers. Treatment with iron chelation is helpful, but requires sometimes daily injections and is very expensive especially in developing countries. In 70% of cases, death is due to heart failure, the onset of which is difficult to predict and often has a rapid downhill course. Therefore our long term aim is to prevent death from heart failure caused by myocardial iron overload in thalassemia by using magnetic resonance (MR) imaging to identify early iron loading, and establish effective and well tolerated myocardial chelation regimes. Thus there is great scope for helping large numbers of sufferers, and also finding more acceptable and cost-effective treatments. In this grant application, we have 4 major aims: first, to understand how iron affects the signal from the MR scanner; second, to optimize MR acquisition sequences so that measurements taken from the images accurately reflect the magnetic relaxation in the tissues; third, to calibrate the MR relaxation measurements against both heart and liver, so that we understand how the measurements made by the scanner relate to the amount of iron in these organs; fourth, to roll-out MR sequences to 6 sites world-wide and validate their use, so that these sites can in principle act as local distributors of the expertise within their own regions, whilst promoting research into improved care in thalassemia. These centers are Philadelphia (USA), Cagliari (Italy), Athens (Greece), Nicosia (Cyprus), Mumbai (India) and Singapore.